The explosion of genetic technology makes identification of individuals with increased cancer risks possible and creates the potential to target cancer screening and prevention efforts. However, the circumstances where genetic predisposition testing is actually an effective and cost-effective clinical strategy are uncertain. A recently described low-penetrance germline mutation in codon I1307K of the APC gene that appears to increase colorectal cancer risk among Ashkenazi Jews underscores the need to critically evaluate when and how genetic testing strategies should be incorporated into clinical cancer prevention. We propose a genetic epidemiologic study among Ashkenazi patients with colorectal cancer and polyps that evaluates the significance of I1307K APC mutations. Our findings will be used to construct a decision analysis model that provides a comprehensive framework for predicting the clinical importance and policy implications of predictive testing for this as well as for other colon cancer predisposing genes. The specific aims to accomplish these goals are: 1. To determine the significance of inherited I1307K APC mutations in a hospital-based cohort of American and Israeli Ashkenazi Jews with colorectal cancer or adenomatous polyps. By evaluating gene frequency and penetrance, this analysis will assess the extent to which inherited I1307K APC mutations increase cancer risk and whether mutation-associated tumors have particular prognostic features. 2. To assess the effectiveness, measured in life-years and quality-adjusted life years, and the cost-effectiveness, of genetic testing for inherited colorectal cancer susceptibility. In particular, we will examine the impact of gene penetrance, gene frequency, age, family history, test characteristics, associated costs, and knowledge motivated screening compliance on the cost-effectiveness of genetic testing strategies. Faculty sponsors in the Division of Population Sciences at the Dana-Farber Cancer Institute will provide the candidate with the guidance critical to accomplishing these aims and to attaining independence as an investigator focused on evaluating the application of genetic technologies to cancer prevention.